The invention concerns a method for detection of a bubble in a liquid, which is placed in a measuring chamber and is in contact with a sensor for measuring the content of a particular gas in the liquid.
The invention also concerns an apparatus for measuring the content of a particular gas in a liquid and comprising a measuring chamber, a sensor connected to the measuring chamber for measuring the content of said gas in the liquid and for providing at least a first and a second measurement, and means for detecting a bubble in the liquid.
The invention is particularly suitable for use in connection with an apparatus for blood gas analysis but it can be used for detection of bubbles in any liquid placed in a chamber for which the partial pressure of a particular gas can be measured at two different pressures.
To be able to carry out a reliable measurement on a blood sample, one of the fundamental demands is that the measurement is performed under controlled conditions. Therefore a blood gas analysis apparatus is often equipped with a lot of self-monitoring equipment so that any error can be reported to the user of the apparatus. In blood measurement, a very serious source of error is bubbles in the blood sample, and particularly bubbles of atmospheric air, because these bubbles may affect the measuring result. If a blood sample contains a bubble, interchange of gasses will occur between the bubble and the blood. The content of e.g. O2 or CO2 in the blood may thus change, and a subsequent measurement will in such a case not reflect the real content of the gases in the blood sample. The problem is especially serious if a bubble is present in the measuring chamber itself, and measurement is performed on the bubble instead of on the blood sample.
In most blood gas analysis apparatuses, several liquid sensors are often placed in the sample channels of the apparatus. These liquid sensors monitor among others how far an introduced sample has travelled in the channels, and if there are any bubbles in the blood sample. In the prior art apparatuses, however, no actual monitoring takes place of whether any bubbles are present in the measuring chamber during the measurement, and therefore it is recommended that the user during measurement inspects the generally visible measuring chamber for the presence of bubbles.
U.S. Pat. No. 4,358,423 discloses a measuring apparatus for blood gas analysis comprising a capillary tube along which measuring and reference electrodes are placed. To detect any air bubbles in the capillary tube, the electrical resistance between preferably three points in the capillary tube is monitored two by two. These points may e.g. be one point in each end of the capillary tube and an intermediate point between the electrodes. The electrical resistances are measured between the intermediate point and each of the end points, respectively. Any presence of a bubble between the intermediate point and any of the end points will increase the resistance substantially. One of the points may be a reference electrode.
U.S. Pat. No. 5,631,552 discloses a method and an apparatus for detection of the presence of air bubbles in a liquid, mainly in blood in connection with dialysis, by monitoring the conductivity of the liquid.
U.S. Pat. No. 5,026,348 discloses a system for monitoring abnormalities in an intravenous catheter, for example air bubbles in the catheter, comprising a piezoelectric vibrator and a piezoelectric detector. The signal registered by the detector is compared with the input signal of the vibrator, and the result indicates the condition of the catheter.
U.S. Pat. No. 5,284,568 discloses a replaceable cartridge for an ion measuring apparatus comprising flow channels in which the air bubbles are detected by measuring the impedance between a bubble sensing element and a ground element.
WO 96/41156 discloses a device for controlling the flow of an intravenous fluid to a patient while monitoring whether there is any bubble in the liquid being delivered to the patient. The liquid runs through a diaphragm with a valve in each end. Bubbles are detected by exposing the diaphragm containing the liquid and with closed valves to a pressure change and then measuring by acoustic resonance any volume change of a measurement gas occupying a box in which the diaphragm is situated. Any volume change of the measurement gas indicates a volume change of the liquid in the diaphragm and thus whether any bubbles are present.
The object of the invention is to provide a method for detecting the presence of a bubble in a liquid in a measuring chamber.
A further object of the invention is to provide an apparatus for performing the method.
The object is achieved by a method which is characterized in performing a first measurement of the content of the particular gas in the liquid at a first pressure in the measuring chamber, changing the pressure in the measuring chamber to a second pressure, performing a second measurement of the content of said gas in the liquid at the second pressure in the measuring chamber, providing an expected result of the second measurement based on the first measurement and assuming that no bubbles are present in the measuring chamber during any of the measurements, and comparing the actual result of the second measurement with the expected result.
The invention is based on the realisation that liquids are substantially incompressible, while gas mixtures comply with Dalton""s Law (the sum of partial pressures is equal to the total pressure).
A gas sensor generally measures the equilibrium partial pressure of the particular gas at the interface between the sensor and the sample phase (gas or liquid) in the measuring chamber. Thus, if a bubble is located near the sensor then the partial pressure of said gas in the bubble may influence the sensor response and consequently the measuring result. If on the other hand only liquid is present near the sensor then an equilibrium partial pressure of said gas in the liquid will determine the sensor response and consequently the measuring result.
The equilibrium partial pressure of the particular gas in the liquid will not be affected by a change of the total pressure in the measuring chamber as the liquid is incompressible. Consequently, if no bubble is present near the sensor, then the partial pressure of said gas at the interface between the sensor and the liquid will not change. In contrast, the partial pressure of a gas, i.e. in a bubble, will be affected by a change of the total pressure in the measuring chamber in accordance with Dalton""s Law. The presence of a bubble near the sensor will accordingly cause a change of the partial pressure of said gas at the interface between the sensor and the fluid. Thus, if the fluid in the measuring chamber is exposed to a pressure change then a comparison of a first measurement before the pressure change and a second measurement after the pressure change will indicate whether a bubble has been present during the measurement.
In reality, a gas phase will always be present above a liquid phase. This gas phase may be located outside the measuring chamber. When a positive pressure is established, gas from the gas phase will diffuse through the phase boundary and into the liquid and increase the equilibrium partial pressure of the gas in the liquid. However, this diffusion is a relatively slow process compared to the time it takes to provide a superimposed pressure change.
This diffusion of gas from the gas phase to the liquid phase will therefore (if no bubble is present) not affect the measurement in the measuring chamber unless a gas sensor with a very long response time is used. The detection of the presence of a bubble in the measuring chamber is thus based on the transient response to a pressure change.
A bubble being present during the first measurement may be forced out of the chamber due to the pressure change before an increased partial pressure can be detected by the sensor during the second measurement. Also in this case the sensor response will change significantly since suddenly the equilibrium partial pressure of the gas in the liquid will be measured by the sensor. A bubble may for instance be forced out of the measuring chamber if a sample channel runs through the measuring chamber and the pressure change is applied from one side of the chamber.
The herein described bubble detection principle can be used to detect bubbles in many types of apparatuses. The only demands are that the sensor/electrode for the particular gas is exposed to sufficiently controlled conditions and that it must be possible to establish a positive pressure or a negative pressure in the measuring chamber of said sensor/electrode. The sensor may thus be based on any measuring principle, such as electrochemical or optical.
An electrochemical oxygen sensor usually measures a flux of oxygen through a gas permeable membrane which is related to the partial pressure of oxygen at the interface between the sensor and sample phase in the measuring chamber. An electrochemical carbon dioxide sensor usually measures an equilibrium concentration of bicarbonate in a sensor solution which is related to the partial pressure of carbon dioxide at said interface.
Optical gas sensors usually measures an effect of said gas, such as absorbance or quenching of luminescence, which is related to the partial pressure of said gas at the interface between the membrane and the sample phase in the measuring chamber. The membrane in such sensors may be a coating of a luminophor on the wall of the measuring chamber.
In the above method the gas to be sensed may for instance be oxygen, carbon dioxide or ammonia, but any gas in a liquid may be measured. A gas sensor may also be provided in a measuring chamber for other analytes with the sole purpose of detecting the presence of bubbles.
The first measurement may be just one or two distinct measurements but is usually performed over a certain measuring period. The measurements may comprise several distinct measurements within the measuring period mentioned or a continuous monitoring within said measuring period. If the first measurement is performed over a measuring period then this may be used to give some information about the response time of the sensor.
The second measurement may also be just a few distinct measurements or be performed over a certain measuring period.
To provide the expected result it is assumed that no bubbles are present. Since liquid is incompressible as mentioned above the expected result will be a continuous course of the sensor signal and the first measurement may provide an estimation for the response signal during the second measurement.
If the first measurement lasts for such a long time that complete equilibrium is obtained, then after a pressure change no substantial change in slope or level will occur, and the expected result will be equal to the parameter in question (slope or level) before the pressure change. If no equilibrium has been obtained during the first measurement, then the expected result may be estimated by means of a curve fit on the basis of previous experience as to the course of the measuring curve. The curve fit may for instance be an approximation to a straight line, a polynomial, an exponential function etc. Finally, it is conceivable to estimate the expected result by multivariable analysis/calibration on the basis of response parameters and sensor parameters.
The comparison criterion for comparing the second measurement with the expected result may for instance be a maximum acceptable deviation from the expected result, for instance a parameter for a curve, such as a slope or a level, or an approximated curve sequence.
The parameter may be expressed by a measured pressure, a measured current from the sensor or another similar expression as is known per se.
The pressure change can be constituted by either positive pressure or negative pressure. The pressure change must have a size which is sufficient to obtain, when a bubble is present in the chamber, a detectable change of response in consequence of the pressure change. The pressure change may e.g. be in the range of 5-100%. It is preferred that the pressure change is in the range of 10-30%. The pressure change is preferably constituted by positive pressure as this is easier to create. The pressure change should not be so big that it causes damage to the sensors. However, the greater a pressure change the greater a deviation from the expected result is observed if a bubble is present.
If a pressure change results in a change of the sensor response, even though no bubble is present, then the estimation of the expected result should compensate for this.
The further object is achieved by an apparatus, which is characterized in that the means for detecting the bubble in the liquid comprise means for changing the pressure in the measuring chamber, means for providing an expected result of the second measurement based on the first measurement and assuming that no bubbles are present in the measuring chamber during any of the measurements, and means for comparing an actual result of the second measurement with the expected result.
The apparatus mentioned may be a blood gas analysis apparatus.
Detection of bubbles is preferably performed in the measuring chambers of the blood gas analysis apparatus in which the content of O2 or CO2 in the sample are determined.
The herein described bubble detection principle is however not limited to blood gas analysis apparatuses, but can also be used in other types of apparatuses. The only demands are that the sensor/electrode for the particular gas is exposed to sufficiently controlled conditions and that it must be possible to establish a positive pressure or a negative pressure in the measuring chamber of said sensor/electrode.
It has been found that there are certain demands to the time constant xcfx84, i.e. the response time of the sensor, in the system. If xcfx84 is too high, the slope of the response curve becomes too small for the system to become stable within the relevant measuring time, and, as previously mentioned, substantial diffusion of gas from the bubble to the liquid may occur. If xcfx84 is too low, the system reacts so fast that equilibrium will be obtained almost instantly and the detection of changes of the slope is very complicated.